NM_000038.6(APC):c.2957A>G (p.Tyr986Cys) AND Familial adenomatous polyposis 1

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Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 29, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000698608.3

Allele description

NM_000038.6(APC):c.2957A>G (p.Tyr986Cys)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.2957A>G (p.Tyr986Cys)

Other names:

p.Y986C:TAT>TGT

HGVS:

NC_000005.10:g.112838551A>G
NG_008481.4:g.151031A>G
NM_000038.6:c.2957A>GMANE SELECT
NM_001127510.3:c.2957A>G
NM_001127511.3:c.2903A>G
NM_001354895.2:c.2957A>G
NM_001354896.2:c.3011A>G
NM_001354897.2:c.2987A>G
NM_001354898.2:c.2882A>G
NM_001354899.2:c.2873A>G
NM_001354900.2:c.2834A>G
NM_001354901.2:c.2780A>G
NM_001354902.2:c.2684A>G
NM_001354903.2:c.2654A>G
NM_001354904.2:c.2579A>G
NM_001354905.2:c.2477A>G
NM_001354906.2:c.2108A>G
NP_000029.2:p.Tyr986Cys
NP_001120982.1:p.Tyr986Cys
NP_001120983.2:p.Tyr968Cys
NP_001341824.1:p.Tyr986Cys
NP_001341825.1:p.Tyr1004Cys
NP_001341826.1:p.Tyr996Cys
NP_001341827.1:p.Tyr961Cys
NP_001341828.1:p.Tyr958Cys
NP_001341829.1:p.Tyr945Cys
NP_001341830.1:p.Tyr927Cys
NP_001341831.1:p.Tyr895Cys
NP_001341832.1:p.Tyr885Cys
NP_001341833.1:p.Tyr860Cys
NP_001341834.1:p.Tyr826Cys
NP_001341835.1:p.Tyr703Cys
LRG_130:g.151031A>G
NC_000005.9:g.112174248A>G
NM_000038.5:c.2957A>G

Protein change:

Y1004C

Links:

dbSNP: rs730881243

NCBI 1000 Genomes Browser:

rs730881243

Molecular consequence:

NM_000038.6:c.2957A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.2957A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.2903A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.2957A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.3011A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.2987A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.2882A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.2873A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.2834A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.2780A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.2684A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.2654A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.2579A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.2477A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.2108A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827283	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 29, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10612827, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827283

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 29, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

UMD (Universal mutation database): a generic software to build and analyze locus-specific databases.

Béroud C, Collod-Béroud G, Boileau C, Soussi T, Junien C.

Hum Mutat. 2000;15(1):86-94.

PubMed [citation]

PMID:: 10612827

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000827283.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces tyrosine with cysteine at codon 986 of the APC protein (p.Tyr986Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 181797). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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